The project is designed to assess individual differences in reactions to drugs as measured by their discriminative stimulus effects. In addition, the differential modulation of these effects by environmental variables will be assessed. This series of studies is designed to understand individual differences in vulnerability as determined by differential reactions to drug effects and differential effects of modulating conditions. The first study was designed to establish the drug discrimination methodology and explore the discriminative stimulus effects of an antihistamine. Twenty normal volunteers were trained to discriminate 75 mg tripelennamine from placebo. There were 33 experimental sessions. At the beginning of each session, subjects filled out mood questionnaires, performed performance tasks, their behavior was rated by observers, and they ingested a capsule. The assessment was repeated at regular intervals. Thirteen of the subjects learned the discrimination and nine of these were tested with additional drugs. Drugs that were identified as tripelennamine by over 75% of the subjects included diazepam and diphenhydramine and there was some evidence of dose related effects. Tripelennamine produced time related increases in diastolic blood pressure and heart rate as well as increases on subjective effects scales indicating sedative like effects. Similar effects were seen with the drugs that substituted although diazepam had different physiological effects. Amphetamine was tested as a negative control but over half of the subjects discriminated both doses as tripelennamine. Its physiological effects were similar to tripelennamine but its subjective effects were placebo like. These results indicate that tripelennamine has subtle or ambiguous discriminative stimulus effects, making it an ideal compound to use in further studies designed to look at vulnerability and modulatory environmental conditions. In two ongoing studies, the same experimental design is being used to assess the influence of instructional control or context. The instructions or context (performance tasks) are designed to bias subjects towards experiencing sedative like effects in one situation or stimulant like effects in another.